# Quantifying cerebellar multi-omic and synaptic features of autism spectrum disorders

> **NIH MH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2026 · $762,566

## Abstract

Project Summary
Strong, longstanding evidence points to important roles for the cerebellum in autism spectrum disorders (ASDs),
yet cerebellar mechanisms remain understudied in ASDs compared to neocortical circuits. Anatomical and
functional studies have pointed, in particular, to changes in the synapses of Purkinje cells, the sole output
neurons of the cerebellum. Purkinje cells were reduced both in number and size in ASD cases, particularly in
the cerebellar vermis and other sub-regions involved in cognition and emotional control. Genes localized to
Purkinje cell synapses were down-regulated. Purkinje cell-specific conditional knockout mice for several ASD
risk genes suggest direct effects of these cerebellar neurons on ASD-related behaviors and synaptic structure
and function. However, cell type-specific transcriptional and epigenomic changes in the cerebellum of individuals
with ASDs remain poorly characterized, and it is unknown whether the synaptic features identified in mouse
models translate to the human condition. Here, we propose comprehensive multi-omic and synaptic imaging
studies to address these knowledge gaps, utilizing a unique post-mortem brain tissue resource from the
University of Maryland Baltimore Brain and Tissue Bank. We will generate single-nuclei multi-omic profiles of
gene expression and chromatin accessibility in ~1.5 million cells from 100 ASD cases and 100 controls. In the
same brain tissue samples, we will perform super-resolution confocal imaging to quantify the density, size, and
nanostructure of Purkinje cell synapses. ~50% of the donors in our cohort will have known causal mutations,
including multiple cases with tuberous sclerosis complex (TSC), Rett syndrome, and Fragile X syndrome,
enabling us to define shared vs. unique features of ASDs with mutations in different genes. Key findings will be
validated in a mouse model of TSC, Tsc1 conditional knockout mice, enabling us to determine which
transcriptomic and synaptic phenotypes ar

## Key facts

- **NIH application ID:** 11305524
- **Project number:** 1R01MH139606-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Seth Abrams Ament; Thomas A Blanpied
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** MH
- **Fiscal year:** 2026
- **Award amount:** $762,566
- **Award type:** 1
- **Project period:** 2026-04-01T00:00:00 → 2030-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11305524

## Citation

> US National Institutes of Health, RePORTER application 11305524, Quantifying cerebellar multi-omic and synaptic features of autism spectrum disorders (1R01MH139606-01A1). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11305524. Licensed CC0.

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